Subthalamic nucleus deep brain stimulation improves sleep in Parkinson's disease patients: a retrospective study and a meta-analysis

BackgroundMost Parkinson's patients suffered from sleep problems. There is increasing evidence that Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) has a positive effect on several sleep parameters, improving overall sleep quality in patients with PD. However, the results are controversial.MethodsWe performed a retrospective study and meta-analysis to assess the Parkinson's disease sleep scale (PDSS) in Parkinson's patients.ResultsWe reviewed our data of patients who underwent STN-DBS, and then extracted five other trials to perform a meta-analysis. The pooled results showed an advantage on post-operative PDSS in both our medical center and pooled results (MD = 20.41, 95% CI = [13.03, 27.79], I² = 61%, P < 0.001). There was a significant difference in Unified Parkinson's Disease Rating Scale (UPDRS)-Ⅲ score between pre and post-operation (MD = −12.59, 95% CI = [−14.70, −10.49], I² = 90%, P < 0.001). What's more, Parkinsonian medication was significantly lower in the post-operative groups after DBS (MD = −314.71, 95% CI = [−468.13, −161.28], I² = 53%, P < 0.001).ConclusionIn the retrospective study and meta-analysis of 6 trials, we found that DBS can significantly increase sleep quality. Furthermore, motor function improved and Parkinsonian medication was significantly decreased postoperatively. The sample size was enough and no further investigations would change the conclusion.     

Long-term effects of concussion on relevancy-based modulation of somatosensory-evoked potentials

ObjectiveThe purpose of this investigation was to better understand the effects of concussions on the ability to selectively up or down-regulate incoming somatosensory information based on relevance.MethodsMedian nerve somatosensory-evoked potentials (SEPs) were elicited from electrical stimulation and recorded from scalp electrodes while participants completed tasks that altered the relevance of specific somatosensory information being conveyed along the stimulated nerve.ResultsWithin the control group, SEP amplitudes for task-relevant somatosensory information were significantly greater than for non-relevant somatosensory information at the earliest cortical processing potentials (N20-P27). Alternatively, the concussion history group showed similar SEP amplitudes for all conditions at early processing potentials, however a pattern similar to controls emerged later in the processing stream (P100) where both movement-related gating and facilitation of task-relevant information were present.ConclusionsPreviously concussed participants demonstrated impairments in the ability to up-regulate relevant somatosensory information at early processing stages. These effects appear to be chronic, as this pattern was observed on average several years after participants’ most recent concussion.SignificanceGiven the role of the prefrontal cortex in relevancy-based facilitation during movement-related gating, these findings lend support to the notion that this brain area may be particularly vulnerable to concussive forces.     

One or two doses of hepatitis A vaccine in universal vaccination programs in children in 2020: A systematic review

BackgroundHepatitis A virus (HAV) is a global health concern as outbreaks continue to occur. Since 1999, several countries have introduced universal vaccination (UV) of children against HAV according to approved two-dose schedules. Other countries have implemented one-dose UV programs since 2005; the long-term impact of this schedule is not yet known.MethodsWe conducted a systematic literature search in four electronic databases for data published between January 2000 and July 2019 to assess evidence for one-dose and two-dose UV of children with non-live HAV vaccines and describe their global impact on incidence, mortality, and severity of hepatitis A, vaccine effectiveness, vaccine efficacy, and antibody persistence.ResultsOf 3739 records screened, 33 peer-reviewed articles and one conference abstract were included. Rapid declines in incidence of hepatitis A and related outcomes were observed in all age groups post-introduction of UV programs, which persisted for at least 14 years for two-dose and six years for one-dose programs according to respective study durations. Vaccine effectiveness was ≥95% over 3–5 years for two-dose programs. Vaccine efficacy was >98% over 0.1–7.5 years for one-dose vaccination. Antibody persistence in vaccinated individuals was documented for up to 15 years (≥90%) and ten years (≥74%) for two-dose and one-dose schedules, respectively.ConclusionExperience with two-dose UV of children against HAV is extensive, demonstrating an impact on the incidence of hepatitis A and antibody persistence for at least 15 years in many countries globally. Because evidence is more limited for one-dose UV, we were unable to draw conclusions on immune response persistence beyond ten years or the need for booster doses later in life. Ongoing epidemiological monitoring is essential in countries implementing one-dose UV against HAV. Based on current evidence, two doses of non-live HAV vaccines are needed to ensure long-term protection.     

如何正确运用t检验——两算术均值比较优效性t检验及SAS实现

本文主要介绍临床试验中优效性检验的概念、假设检验、界值设定和样本量的估计以及成组设计一元定量资料优效性t检验的SAS实现。通过实例展示SAS在优效性t检验中的应用,分别基于两种数据结构(原始定量数据和样本含量、均值、标准差数据)进行操作,对结果进行解释并作出结论。     

Immunogenicity and safety of MF59-adjuvanted quadrivalent influenza vaccine versus standard and alternate B strain MF59-adjuvanted trivalent influenza vaccines in older adults

ObjectiveEvaluate whether adjuvanted quadrivalent influenza vaccine (aQIV) elicits a noninferior immune response compared with a licensed adjuvanted trivalent influenza vaccine (aTIV-1; Fluad™) and aTIV-2 containing an alternate B strain, examine whether aQIV had immunological superiority for the B strain absent from aTIV comparators, and evaluate reactogenicity and safety among adults ≥65 years.MethodsIn a multicenter, double-blind, randomized controlled trial, adults ≥65 years were randomized 2:1:1 to vaccination with aQIV (n = 889), aTIV-1 (n = 445), or aTIV-2 (n = 444) during the 2017-2018 influenza season. Immunogenicity was assessed by hemagglutination inhibition (HI) assay conducted on serum samples collected before vaccination and 21 days after vaccination for homologous influenza strains.ResultsaQIV met non-inferiority criteria for geometric mean titer ratios (GMT ratios) and seroconversion rate (SCR) differences against aTIV. The upper bounds of the 2-sided 95% confidence interval (CI) for GMT ratios were <1.5 for all 4 strains (A/H1N1 = 1.27, A/H3N2 = 1.09, B-Yamagata = 1.08, B-Victoria = 1.08). The upper bounds of the 95% CI of the SCR differences were <10% for all 4 strains (A/H1N1 = 7.76%, A/H3N2 = 4.96%, B-Yamagata = 3.27%, B-Victoria = 2.55%). aQIV also met superiority criteria (upper bound of 95% CI for GMT ratios <1 and SCR differences <0) for B strain absent from aTIV comparators (B-Yamagata GMT ratio = 0.70, SCR difference = −8.81%; B-Victoria GMT ratio = 0.78, SCR difference = −8.11%). aQIV and aTIV vaccines were immunogenic and well-tolerated. The immunological benefit of aQIV was also demonstrated in age subgroups 65–74 years, 75–84 years, and ≥85 years and in those with high comorbidity risk scores. Reactogenicity profiles were generally comparable.ConclusionaQIV induces a similar immune response as the licensed aTIV vaccine against homologous influenza strains and has a comparable reactogenicity and safety profile. Superior immunogenicity against the additional B strain was observed, indicating that aQIV could provide a broader protection than aTIV against influenza in older adults (NCT03314662).     

Evaluation of five circulating strains of variant infectious bursal disease virus (varIBDV) for their immunogenicity as broiler breeder vaccines and protective efficacy in neonatal broiler chicks

The majority of infectious bursal disease virus (IBDV) strains circulating in the broiler chicken industry in Canada are variant strains (varIBDV). Despite high levels of maternally derived antibodies (MtAb), the circulating varIBDVs can establish infection and cause severe immunosuppression in broiler chicks. The objective of this study was to evaluate circulating varIBDVs as broiler breeder vaccine candidates and investigate their protective efficacy against varIBDV challenge in their progeny chicks. Six groups of breeders (20 females/group) were vaccinated with varIBDV strains, SK09, SK10, SK11, SK12, and SK13 or saline at the age of 13 weeks and antibody response was determined by ELISA at 3–7-, and 20- weeks post-vaccination. We also included commercial chicks for the comparison. Results showed that SK-09 is the most antigenic strain, followed by SK-10, SK-12, and SK-13. In contrast, SK-11 showed the lowest antibody response, and over time, antibody titers steadily decreased. Eggs from breeders were collected at 21-week post-vaccination and incubated to produce their respective progenies. The serum antibody titer in day-old chicks showed a successful MtAb transfer. Progeny chicks (n = 40/group) were orally challenged with varIBDV-SK-09 strain at 6 days of age and serum antibody titer (19 d and 35 d of age), bursa to body weight ratio (19 d and 35 d of age), bursal viral load (9 d and 19 d of age) was examined to assess the protection against IBDV. Following the challenge, we found a significant increase in the antibody titers in MtAb-free and commercial vaccine groups than in the varIBDV groups, both at 19 d and 35 d of age. The BBW ratio and viral load data indicated a significant homologous and heterologous protection against varIBDV-SK-09 challenge by SK-09 and SK-10 MtAbs, respectively. Overall, this study demonstrated the feasibility of developing breeder vaccines using circulating varIBDV as candidate vaccine antigens.     

Randomized,double-blind,placebo-controlled,safety and immunogenicity study of 4 formulations of Anthrax Vaccine Adsorbed plus CPG 7909 (AV7909) in healthy adult volunteers

A new anthrax vaccine that could accelerate the immune response and possibly reduce the number of injections needed for protection would be desirable in a post-exposure setting.